An in vitro model of "pannus" formation in rheumatoid arthritis (RA) has been developed in which dissociated suspensions of T lymphocytes and synoviocytes obtained from RA synovial samples are cultured in vitro to produce organized tissue outgrowths that have the histological appearance of "pannus". The culture conditions and cells which are required for the outgrowths will be studied in detail, including the nature of the mycobacterial protein antigen used to initiate the culture and the subsets of T cells which contribute to synoviocyte growth and secretion of extracellular matrix. The relationship of the outgrowths to RA will be analyzed by mixing experiments in which fresh or cloned RA T cells will be mixed with non-RA synoviocytes and vice versa. The cytokines transcribed and secreted by the T cells and synoviocytes will be identified by analysis of mRNA using the polymerase chain reaction and by bioassays. The contribution of the cytokines to tissue outgrowth will be determined by appropriate use of inhibitors and recombinant molecules in the cultures. Finally, the use of this model as a predictor of effective therapies in RA will be examined by adding known effective drugs to the culture system in an attempt to inhibit tissue outgrowth. If the model can detect current effective drugs, then it may be used as a screening device for new drugs in RA.